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Register a new userSelf-tolerance and autoimmunity in a minimal model of the idiotypic network
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We consider self-tolerance and its failure -autoimmunity- in a minimal mathematical model of the idiotypic network. A node in the network represents a clone of B-lymphocytes and its antibodies of the same idiotype which is encoded by a bitstring. The links between nodes represent possible interactions between clones of almost complementary idiotype. A clone survives only if the number of populated neighbored nodes is neither too small nor too large. The dynamics is driven by the influx of lymphocytes with randomly generated idiotype from the bone marrow. Previous work has revealed that the network evolves towards a highly organized modular architecture, characterized by groups of nodes which share statistical properties. The structural properties of the architecture can be described analytically, the statistical properties determined from simulations are confirmed by a modular mean-field theory. To model the presence of self we permanently occupy one or several nodes. These nodes influence their linked neighbors, the autoreactive clones, but are themselves not affected by idiotypic interactions. The architecture is very similar to the case without self, but organized such that the neighbors of self are only weakly occupied, thus providing self-tolerance. This supports the perspective that self-reactive clones, which regularly occur in healthy organisms, are controlled by anti-idiotypic clones. We discuss how perturbations, like an infection with foreign antigen, a change in the influx of new idiotypes, or the random removal of idiotypes, may lead to autoreactivity and devise protocols which cause a reconstitution of the self-tolerant state. The results could be helpful to understand network and probabilistic aspects of autoimmune disorders.
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We consider the problem of self tolerance in the frame of a minimalistic model of the idiotypic network. A node of this network represents a population of B lymphocytes of the same idiotype which is encoded by a bit string. The links of the network connect nodes with (nearly) complementary strings. The population of a node survives if the number of occupied neighbours is not too small and not too large. There is an influx of lymphocytes with random idiotype from the bone marrow. Previous investigations have shown that this system evolves toward highly organized architectures, where the nodes can be classified into groups according to their statistical properties. The building principles of these architectures can be analytically described and the statistical results of simulations agree very well with results of a modular mean field theory. In this paper we present simulation results for the case that one or several nodes, playing the role of self, are permanently occupied. We observe that the group structure of the architecture is very similar to the case without self antigen, but organized such that the neighbours of the self are only weakly occupied, thus providing self tolerance. We also treat this situation in mean field theory which give results in good agreement with data from simulation.
We develop a modular mean field theory for a minimalistic model of the idiotypic network. The model comprises the random influx of new idiotypes and a deterministic selection. It describes the evolution of the idiotypic network towards complex modular architectures, the building principles of which are known. The nodes of the network can be classified into groups of nodes, the modules, which share statistical properties. Each node experiences only the mean influence of the groups to which it is linked. Given the size of the groups and linking between them the statistical properties such as mean occupation, mean life time, and mean number of occupied neighbors are calculated for a variety of patterns and compared with simulations. For a pattern which consists of pairs of occupied nodes correlations are taken into account.
We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.
We propose a strange-attractor model of tumor growth and metastasis. It is a 4-dimensional spatio-temporal cancer model with strong nonlinear couplings. Even the same type of tumor is different in every patient both in size and appearance, as well as in temporal behavior. This is clearly a characteristic of dynamical systems sensitive to initial conditions. The new chaotic model of tumor growth and decay is biologically motivated. It has been developed as a live Mathematica demonstration, see Wolfram Demonstrator site: http://demonstrations.wolfram.com/ChaoticAttractorInTumorGrowth/ Key words: Reaction-diffusion tumor growth model, chaotic attractor, sensitive dependence on initial tumor characteristics
The immune system protects the body against health-threatening entities, known as antigens, through very complex interactions involving the antigens and the systems own entities. One remarkable feature resulting from such interactions is the immune systems ability to improve its capability to fight antigens commonly found in the individuals environment. This adaptation process is called the evolution of specificity. In this paper, we introduce a new mathematical model for the evolution of specificity in humoral immunity, based on Jernes functional, or idiotypic, network. The evolution of specificity is modeled as the dynamic updating of connection weights in a graph whose nodes are related to the networks idiotypes. At the core of this weight-updating mechanism are the increase in specificity caused by clonal selection and the decrease in specificity due to the insertion of uncorrelated idiotypes by the bone marrow. As we demonstrate through numerous computer experiments, for appropriate choices of parameters the new model correctly reproduces, in qualitative terms, several immune functions.
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